Effect of ethanol and cocaine treatment on the immune system of v-Ha-ras-transgenic mice |
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| Affiliation: | 1. Arizona Prevention Center, College of Medicine, University of Arizona, Tucson, AZ 85724, U.S.A.;1. Protein & Peptide Pharmaceutical Laboratory, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China;2. Department of Hematology and Medical Oncology, Emory University, Atlanta, Georgia, USA;1. Institute of Natural Resources and Ecology, Heilongjiang Academy of Sciences, Sino-Finnish Center for Berry Research and Technology, Harbin 150040, PR China;2. School of Life Sciences, Zhengzhou University, Zhengzhou 450001, PR China;3. Harbin Institute of Technology, 73 Huanghe Road, Nangang District, Harbin 150090, PR China;4. Food Chemistry and Food Development, Department of Biochemistry, University of Turku, FI-20014 Turku, Finland;1. Department of Molecular Medicine, Tissue Injury Defense Research Center, School of Medicine, Ewha Womans University, Seoul, South Korea;2. Natural Products Research Institute, Korea Institute of Science and Technology, Ganneung, South Korea;3. Department of Pharmacology, Tissue Injury Defense Research Center, School of Medicine, Ewha Womans University, Seoul, South Korea |
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| Abstract: | The objective was to investigate if the presence of the v-Ha-ras oncogene could induce immune changes different to the ones observed in normal mice. Therefore, we decided to use Oncomice, the transgenic mice with an activated v-Ha-ras oncogene under the control of the mouse mammary tumor virus-promoter, and their normal inbred counterparts, FVB mice. Both strains of mice were fed the Lieber-DeCarli liquid diet with ethanol or the isocaloric control diet and were injected daily with cocaine or saline. The percentage and absolute number of T and B lymphocytes in the spleen and thymus were determined. The in vitro production of TNF-α (tumor necrosis factor-α), IL-2 (interleukin-2) and IFN-γ (interferon-gamma) by spleen cells, and the levels of serum sIL-2R (soluble IL-2 receptor) were also measured. Oncomice fed the Lieber-DeCarli ethanol diet or receiving either saline or cocaine injections presented a higher tumor incidence than Oncomice receiving the control diet. A reduced total number of thymocytes as well as absolute number of cells in all the subsets was found in Oncomice. Moreover, a decreased percentage of CD8+ cells was also observed in Oncomouse spleens. These features were even more marked in ethanol-treated Oncomice. Higher serum sIL-2R levels were observed in Oncomice, especially in mice treated with ethanol or cocaine. The results suggest that the oncogene product, P21ras, plays an important role in dysregulating the immune system and hence in favoring tumorigenesis. |
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